Generally, human body contains about 100,000 to 150,000 hairs. Hairs grow and fall out through the stages of anagen, catagen and telogen with different cycles from one another. This growth cycle repeats with a period of 3 to 6 years, and thus, about 50 to 100 hairs fall out every day. Alopecia refers to a condition which occurs as hairs in anagen are decreased and hairs in catagen and telogen are increased. Alopecia is mainly caused by excessive secretion of androgen, one of male sex hormones, in hair root and sebaceous gland, which intensively stimulates hair follicle cells and contracts hair follicles, thereby to retard hair growth. Other known causes of alopecia include insufficient nutrition due to local blood flow disturbance, excessive secretion of sebum, malfunction of scalp due to peroxides, bacteria, etc., lapse of neurosis due to intensive external stress and chronic diseases, and so on. Interest in hair regeneration is increasing as the generation of alopecia becomes more serious by overwork, environmental pollution, side effects due to misuse and abuse of addictive drugs, scalp blood flow disturbance due to permanent, dyeing, use of mousse, spray, etc., genetic factors and so on. Recently, alopecia in young age is increased including female obese alopecia as well as male pattern alopecia. Therefore, various kinds of hair regrowth or growth agents are commercialized for improving alopecia. Commercially available hair regrowth or growth agents include vasodilators such as capronium chloride, minoxidil, etc., hormone drugs for inhibiting action of male sex hormone such as estrogen, estradiol, etc. and inhibitors of activity of male sex hormone such as pentadecanoic acid, finasteride, etc.
The most commonly used agent for treatment or prevention of alopecia and for promotion of hair regrowth is a minoxidil-containing formulation manufactured by Upjohn Co., Ltd., which is disclosed in U.S. Pat. No. 4,596,812. Minoxidil is one of two hair regrowth ingredients which have been approved by the U.S. Food and Drug Administration (FDA). Minoxidil was originally developed as a drug for treating hypertension for the purpose of reducing blood pressure. However, hair regrowth was observed as a side effect, and thus, this became more famous as a hair regrowth agent. Although a mechanism by which minoxidil acts as a hair regrowth agent has not yet been clearly understood, minoxidil is believed to improve nutrition to hair root by increasing blood flow from vasodilatory action, thereby to promote hair growth. A recent report indirectly supports this increased blood flow model (Br. J. of Dermatol., 1998; 138; 407-411) that minoxidil increases the expression of vascular endothelial growth factor (VEGF), a growth factor associated with vasodilation in dermal papilla, a major cell constituting hair root. In addition to vasodilatory action of minoxidil in hair regrowth, it has been reported that minoxidil promotes activation of dermal papilla cells in hair root cultivated in vitro (Skin Pharmacol., 1996; 9; 3-8) and growth of hair follicles in tissue culture (J. Invest. Dermatol., 1989; 92; 315-320). This suggests that minoxidil may act directly on hair root as a growth factor. Furthermore, finasteride, a main ingredient of Propecia having been recently commercialized by Merck, inhibits conversion of male sex hormone, testosterone, into dihydrotestosterone (DHT), the more potent male hormone than testosterone, by action of 5α-reductase. On December of 1997, 1 mg tablet was approved by FDA as a hair-regrowth agent for treatment of male pattern alopecia, and is now commercially available. In clinical use, it has been proved to have a significant effect (J. Am. Acad. Dermatol., 1998; 39; 578-589). In addition, there have been many efforts to promote hair regrowth by spreading to scalp or orally administering extracts of various natural substances or herbs.
However, minoxidil and capronium chloride, which have been widely used to prevent and treat alopecia, have insufficient clinical effects. Hormone drugs for inhibiting action of male sex hormone or inhibitors of activity of male sex hormone have insufficient clinical effects, or may inhibit male sexual function as a side effect. In addition, they may have a problem in safety in human body since active ingredients thereof are synthetic compounds and they do not show sufficient effect in hair regrowth or hair growth. In case of hair improving compositions containing various natural extracts, their functional mechanism has not been clearly revealed, and their effects have not been sufficiently proved. They also has problems that their active ingredients have low absorbability and poor skin feeling such as stickiness on scalp, and cause skin troubles.
In order to overcome limits of hair regrowth agents due to side effects of chemical drugs, implantation of hairs on scalp has been performed, but it takes much cost and long time to implant hairs one by one. Therefore, implantation is just temporary, but is insufficient as a fundamental treatment.
Hairs consist of three parts: cuticle, cortex and medulla. The cortex surrounding the medulla is the thickest part of hairs (about 80 to 90% of the total thickness of hairs), and includes granules called as melanosome consisting of melanin, lipid membrane, tyrosinase related protein-1 (TRP-1), TRP-2 and other proteins. Melanin is synthesized at melanosome which is an organelle within melanocytes, and is delivered to neighboring keratinocytes through dendrons of melanocytes. In synthetic pathway of melanin, tyrosine, an amino acid, is oxidized to DOPA and the DOPA is further oxidized to dopaquinone, in which step tyrosinase is involved. Subsequent reactions are auto-oxidative, but it is known that enzymes such as TRP-1 and TRP-2 are involved to accelerate the reactions. Brightness of hair is determined by factors such as types and distributed amounts of eumelanin and pheomelanin formed from tyrosine, and thus, each people has unique hair color. Eumelanin is the most common and the darkest pigment, and forms brown or black hair. Pheomelanin has bright color and forms blonde hair. White hair is caused as melanogenesis is stopped at dopaquinone followed by keratinization, and oxidation does not occur since tyrosinase cannot be produced. White hair is more clearly observed in human races having black or brown hairs, and is a kind of aging that occurs as melanogenesis is stopped in melanocytes. In addition to such senile white hair, white hair may further include premature gray hair, hereditary poliosis, acquired poliosis due to vitiligo vulgaris, alopecia areata, etc., white hair due to drugs and chemicals, poliosis due to stress, white hair due to autoimmune diseases, poliosis due to malnutrition and unbalanced nutrition, poliosis due to renal dysfunction, and so on.
Gene therapy may treat hereditary white hair, and Treatment of a disease may treat white hair due to the disease. In other cases, uses of knotgrass, Sophora flavescens, sea weed fusiforme, Rehmannia radix, Rehmanniae radix preparata, mulberry, plantain oil, bamboo oil, bear oil, etc. have been known as folk remedies, but they cannot be expected to have significant effects.
Rare earth elements are trace metal elements, which are contained at about 0.016% in the earth's crust, and refer to minerals including 17 elements, 15 elements of atomic numbers from 57 to 71 (La, Ce, Pr, Nd, Pm, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu) and 2 elements of group 3A (Sc, Y) in the periodic table of elements. Rare earth element may exist in the form of salt in which it is ionically bonded with its counter-ion, for example, in the form of sulfate, nitrate, carbonate, acetate, phosphate, chloride, etc., or in the form of oxide including hydroxide. Rare earth elements are very useful even though they have been found only two hundred years ago, and are not still well-known to public. Since rare earth elements have unique physical and chemical effects due to their unique electronic structures, they have been used in machinery, petrochemistry, photochemistry, etc. as permanent magnet, superconductor or fluorophore, and have been recently tried to be applied in various fields of agriculture, forestry, livestock industry, etc. Furthermore, as biological effects, rare earth elements promote photosynthetic action and chlorophyll production in higher plants; promote shoot formation; increase root vitality; activate respiratory function; promote nutrient transport in plant body; control moisture; promote cell division, hormone transfer, and absorption and transport of nutrients; activates metabolism; increases synthesis of protein and RNA in leaves, etc. In addition, they retard aging of leaves, increase protein contents in green algae, and promote synthesis of protein and chlorophyll by promoting photosynthesis and oxygen releasing activity. La3+ is known to increase activity of (Na+, K+)-ATPase and Mg2+-ATPase in cell membrane of human erythrocytes, and thus, strengthen functions of Ca2+ ion in human body (The journal of Biological Chemistry, 1986; 261(20); 9552-9557). Some of rare earth elements are known to have antibacterial (Chem. Pharm. Bull, 2003; 51(5); 494-498) and antioxidative activities by preventing generation of reactive oxygen species (Biochemical and Biophysical Research Communication, 2006; 2; 86-91). Further, some of rare earth elements are known to activate cells, promote blood circulation, strengthen metabolism and increase regenerability of tissues by their interaction with far infrared ray as alkaline ions, thereby preventing fatigue and aging. They are also known to increase weight and feed conversion ratio (FCR) in growing fat pigs (J. Anim. Physiol. a. Anim. Nutr., 2001; 85; 263-270). Furthermore, it was found that rare earth elements are low toxic, absorbed by a very small amount through digestive organs, scarcely accumulated in body, and not teratogenic, mutagenic or carcinogenic (Environmental Health Perspectives, 1996; 104; 85-95).
Korean Patent No. 569,083 discloses a UV shielding agent comprising metal oxide doped cerium oxide in which metal ion having larger ion radius than that of Ce4+ and/or lower valence metal ion than Ce4+ are doped, and a cosmetic composition containing the same. It also describes that the cosmetic composition may be used as a hair cosmetic. However, it relates to the metal oxide doped cerium oxide but does not relate to uses of rare earth elements, or salts or mixtures thereof. U.S. Pat. No. 5,112,360 discloses a hair dye comprising 5,6-dihydroxyindole and/or an indole derivative, and at least one salt of rare earth element. However, it relates to hair dyeing effect of the composition consisting of indole compound and salt of rare earth element, and neither taught nor suggested that rare earth element alone directly promotes the formation of black hairs, when applied to hair or hair root. In addition, Japanese Patent Laid-Open No. 2003-137749 (published on May 14, 2003) discloses a hair concealer charged in a spray container, manufactured by the process in which natural ore containing a radioactive rare earth element such as lanthanum (La), neodymium (Nd), samarium (Sm), gadolinium (Gd) and lutetium (Lu) is pulverized into a particle diameter of ≦5 μm, the pulverized natural ore is mixed with a colorant in a viscous liquid binder composed of an alcoholic solvent and a solute soluble in the solvent to give a mixture, and then, the mixture is charged into a spray container. This Laid-Open Patent relates to a hair concealer with which a hair deficient region is covered so as to be visually hairy, and environments around scalp are improved for regeneration and growth of hairs. It describes that β ray emitted from radioactive rare earth elements attached to scalp after spraying forms anions, thereby promoting blood circulation to promote regeneration and growth of hairs. However, it relates to promotion of blood circulation by β ray emission from natural radioactive rare earth elements, and hair concealing or growth effect derived therefrom, but has no mention on promotion of cell proliferation, inhibition of TGF-βexpression, promotion of VEGF expression, promotion of activity and expression of tyrosinase, and promotion of melanogenesis by rare earth elements.